Amdoxovir is a guanosine analogue nucleoside reverse transcriptase inhibitor that is active in vitro against both HIV-1 and HBV. It is deaminated intracellularly by adenosine deaminase to dioxolane guanine (DXG). DXG-triphosphate, the active form of the drug, has greater activity than DAPD-triphosphate. Amdoxovir is under development (phase II study) for the treatment of HIV infection. Five subjects demonstrated lens opacities during the study, although baseline evaluations were not performed. Clinical studies of amdoxovir are currently on hold pending additional safety data.

LAGOCICLOVIR is a nucleoside reverse transcriptase inhibitor with activity against human immunodeficiency virus and hepatitis B virus.

Aranotin, a metabolite of Arachniotus aureus, possesses the antiviral and antibiotic properties. It inhibits viral RNA synthesis against strains of rhino-, coxsackie, polio- and parainfluenza viruses.

Alovudine (3’ -deoxy-3’ fluorothymidine) is a nucleoside reverse transcriptase inhibitor (NRTI) initially tested in the early 1990s, before the era of combination therapy and before the availability of plasma viral load measurement. Initial toxicity studies showed that the primary target organ of toxicity was the bone marrow. A lack of clear advantages in activity over zidovudine, the only drug approved in the early 1990s, and the potential for bone marrow toxicity caused alovudine development to be stopped [6]. However, later in vitro studies found alovudine to be very effective at suppressing several NRTI-resistant HIV-1 mutants, including isolates with multiple thymidine-associated mutations (TAMs) or multi-NRTI-resistance mutations. Alovudine at a dose of 7.5 mg/day added to a failing antiretroviral combined regimen in patients with isolates resistant to other NRTIs yielded a median viral load decline after a 4-week period in patients not receiving concomitant stavudine. In July 2003, Medivir out-licensed it's HIV antiviral MIV-310 to Boehringer Ingelheim. Under the terms of the agreement, Boehringer Ingelheim will make upfront and milestone payments to Medivir totaling up to 122 million euro in the event that all development and performance milestones are met. In March 2005, Boehringer Ingelheim recently completed a clinical trial of MIV-310 (alovudine) in HIV/AIDS. The efficacy exhibited by MIV-310 at the doses tested showed antiviral activity but did not achieve the target level of efficacy which had previously been defined. Boehringer Ingelheim, therefore, decided to stop the development of this investigational drug.

Lersivirine (UK-453,061) is a novel second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). It binds reverse transcriptase in a distinct way leading to a unique resistance profile. Lersivirine is a second-line NNRTI, which was investigated in a Phase IIb clinical trial. Lersivirine has shown encouraging virologic efficacy in a Phase IIa monotherapy study in NNRTI-naive patients. In a Phase IIb clinical trial in ART naive patients, clinical efficacy of lersivirine was compared with efavirenz, each administered together with tenofovir disoproxil fumarate/emtricitabine. After 48 weeks, lersivirine exhibited a slightly lower virologic response but similar immunologic efficacy. However, the trial was not powered for formal hypothesis testing of noninferiority of lersivirine. The development of lersivirine was recently stopped because the developing company determined that the compound would not provide an improvement over existing NNRTIs.

Sovaprevir (formerly ACH-1625) is an oral, once-daily, small molecule inhibitor of HCV protease being developed by Achillion Pharmaceuticals for the treatment of Hepatitis C. ACH-1625 is a linear peptidomimetic inhibitor that non-covalently binds to HCV NS3 protease with high potency and specificity. Short-term monotherapy of HCV genotype-1 infection with ACH-1625 was found to be safe and resulted in ≥3.3 log(10) IU/ml mean viral load reduction. Sovaprevir was developed as a therapy for patients with chronic HCV. Approximately 550 patients already have been treated with the drug in two phase 2 studies with 12-week treatment programs. One study included treatment with sovaprevir combined with pegylated interferon and ribavirin, and the other monitored the use of sovaprevir in combination with ACH-3102, Achillions second-generation NS5A inhibitor. In the second study, all of the patients with HCV genotype 1b achieved sustained virologic response.

Vapendavir (BTA-798) is an orally active capsid-binding inhibitor. It is a potent, orally bioavailable, broad spectrum inhibitor of the large group of HRVs. Vapendavir binds tightly to VP1s canyon and disrupts the ability of the capsid to bind to a specific cell surface receptor. This further inhibits the release of the viral RNA into the cell cytoplasm during the viral uncoating process (removing the lipid bilayer), thereby disrupting viral replication. Vapendavir is designed to be dosed orally. Vapendavir is in phase II clinical trials for the treatment of rhinovirus-induced aggravation of pre-existing asthma or COPD. Vapendavir has shown significant results in proof-of-concept studies. Thus far, from the Phase 1/2 studies conducted, vapendavir has demonstrated a desirable clinical pharmacology profile with high bioavailability, linear pharmacokinetic profile, remained unaffected by concomitant medications, and was not exclusively metabolized.

Palinavir (formerly BILA2011BS) is a potent inhibitor of the human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) proteases and was studied for the treatment of HIV infections. However, information about the current development of this drug is not available.

Droxinavir is hydroxyethylurea human immunodeficiency virus type 1 (HIV-1) protease inhibitor. Position 88 of HIV-1 protease gene plays a key role in the interaction between droxinavir and the protease molecule. A mutation in this position, located outside the active site, confers resistance to the hydroxyethylurea inhibitor droxinavir. The V82A and N88S substitutions conferred droxinavir resistance on HIV-1 recombinant variants. Positions 82 and 88 are reported to be variable in natural populations isolated from patients who have not been treated with protease inhibitors. Droxinavir had been in preclinical phase for the treatment of HIV-1 infection. However, this study was discontinued.

Amenamevir is an antiviral agent discovered by Astellas Pharma Inc. and is considered to exert anantiviral effect by inhibiting the activity of the helicase-primase complex, which is involved in DNA replication of herpes virus. It is a helicase-primase inhibitor against herpes simplex virus 1 (HSV-1), HSV-2, and varicella zoster virus. Amenamevir inhibited the in vitro replication of HSV-1 with a mean 50% effective concentration (EC(50)) of 14 ng/ml. Amenamevir was approved in Japan for the treatment of Herpes zoster.